Pain
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Prior research supports the validity and short-term test-retest stability of 4 commonly used scales for assessing pain intensity (Visual Analogue Scale [VAS], 6-point Verbal Rating Scale [VRS-6], Numerical Rating Scale [NRS-11], and Face Pain Scale-Revised [FPS-R]). However, the relative stability and ability of these measures to detect changes in pain intensity over longer time periods have not yet been examined, although knowledge regarding these psychometric issues is important for selecting from among these measures. To address this knowledge gap, we administered these scales assessing worst and average pain intensity to 250 chronic pain outpatients on 2 occasions, a little over 6 weeks apart on average. ⋯ However, the psychometric properties of the scales were not influenced by education level. Overall, the NRS-11 emerged as showing the most sensitivity and stability. The FPS-R seems to be a good second choice to consider for samples of individuals who might have difficulty understanding or using the NRS-11.
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Ample data support a prominent role of peripheral T-type calcium channels 3.2 (Ca V 3.2) in generating pain states. Development of primary sensory neuron-specific inhibitors of Ca V 3.2 channels is an opportunity for achieving effective analgesic therapeutics, but success has been elusive. Small peptides, especially those derived from natural proteins as inhibitory peptide aptamers (iPAs), can produce highly effective and selective blockade of specific nociceptive molecular pathways to reduce pain with minimal off-target effects. ⋯ Two prototype Ca V 3.2iPAs (iPA1 and iPA2) derived from the IDRs of Ca V 3.2 intracellular loops 2 and 3, respectively, were expressed selectively in the primary sensory neurons of dorsal root ganglia in vivo using recombinant adeno-associated virus (AAV), which produced sustained inhibition of calcium current conducted by Ca V 3.2/T-type channels and significantly attenuated both evoked and spontaneous pain behavior in rats with neuropathic pain after tibial nerve injury. Recordings from dissociated sensory neurons showed that AAV-mediated Ca V 3.2iPA expression suppressed neuronal excitability, suggesting that Ca V 3.2iPA treatment attenuated pain by reversal of injury-induced neuronal hypersensitivity. Collectively, our results indicate that Ca V 3.2iPAs are promising analgesic leads that, combined with AAV-mediated delivery in anatomically targeted sensory ganglia, have the potential to be a selective peripheral Ca V 3.2-targeting strategy for clinical treatment of pain.
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Peripheral sensory neurons located in dorsal root ganglia relay sensory information from the peripheral tissue to the brain. Satellite glial cells (SGCs) are unique glial cells that form an envelope completely surrounding each sensory neuron soma. This organization allows for close bidirectional communication between the neuron and its surrounding glial coat. ⋯ Here, we present a detailed characterization of the transcriptional profile of SGC in mice, rats, and humans at the single cell level. Our findings suggest that key features of SGC in rodent models are conserved in humans. Our study provides the potential to leverage rodent SGC properties and identify potential targets in humans for the treatment of nerve injuries and alleviation of painful conditions.
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Complex regional pain syndrome (CRPS) is an inadequate local response after a limb trauma, which leads to severe pain and autonomic and trophic changes of the affected limb. Autoantibodies directed against human β2 adrenergic and muscarinic M2 receptors (hβ2AR and hM2R) have been described in CRPS patients previously. We analyzed sera from CRPS patients for autoantibodies against hβ2AR, hM2R, and endothelial cells and investigated the functional effects of purified IgG, derived from 13 patients with CRPS, on endothelial cells. ⋯ Regarding second messenger pathways, CRPS-IgG induced ERK1/2, p38, and STAT1 phosphorylation, whereas AKT phosphorylation was decreased at the protein level. In addition, increased expression of adhesion molecules (ICAM-1 and VCAM-1) on the mRNA level was induced by CRPS-IgG, thus inducing a pro-inflammatory condition of the endothelial cells. Our results show that patients with CRPS not only develop autoantibodies against hβ2AR and hM2R, but these antibodies also interfere with endothelial cells, inducing functional effects on these in vitro, and thus might contribute to the pathophysiology of CRPS.
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Osteoarthritis pain affects the lives of a large number of people around the world. Understanding other people's experience is integral to effective care, and qualitative research can have an important part to play in education and good clinical practice. We aimed to systematically search for, identify, and synthesise qualitative research exploring the experience of living with osteoarthritis to incorporate this knowledge into an educational resource. ⋯ Our findings highlight the profound impact that osteoarthritis can have on people's lives and the struggle to hold onto a sense of self. They indicate that recognising these losses, and taking osteoarthritis seriously, is an integral part of effective health care. This finding may be transferable beyond this condition.